Time-averaged disease activity fits better joint destruction in rheumatoid arthritis

Disease activity of rheumatoid arthritis (RA), evaluated as Disease Activity Score (DAS), is associated with joint destruction. Since joint destruction reflects the history of disease activities, we hypothesized that time-averaged disease activity would better correlate with joint destruction than one-time disease activity. We recruited RA patients in IORRA (n = 557) and KURAMA (n = 204) cohorts, and calculated time-averaged DAS28 to model a modified Sharp/van der Heijde score (SHS). We evaluated the fitting of the model using time-averaged DAS28 among 1000 models in which we randomly picked up onetime DAS28. We also used clinical disease activity index (CDAI) or data in the BeSt study (European population). After conditioning on autoantibody and disease duration, time-averaged DAS28 showed significant improvement of model fitting compared with one-time DAS28 in both cohorts (p = 0.001 and 0.034, respectively). Time-averaged CDAI also showed a better fit. Integration of multiple DAS fit SHS better in the BeSt study. A good fit of time-averaged DAS could be observed using five to six time points of DAS. In conclusion, time-averaged disease activity fits the joint destruction model better than onetime disease activity. Usage of time-averaged disease activity as a covariate would increase the power of studies to identify novel correlates of joint destruction.